@article{smith_berglund_robertson_schnabel_mcmullen_gilger_oh_2023, title={Effect of gentamicin on CD3+ T‐lymphocyte proliferation for treatment of equine recurrent uveitis: An in vitro study}, volume={26}, ISSN={1463-5216 1463-5224}, url={http://dx.doi.org/10.1111/vop.13098}, DOI={10.1111/vop.13098}, abstractNote={OBJECTIVE The objective of the study was to determine the effect of gentamicin on CD3+ T-lymphocyte proliferation and cell viability using an in vitro cell culture model as a means of investigating the mechanism of action of low-dose intravitreal gentamicin injection. ANIMALS STUDIED Three adult horses with no evidence of ophthalmic or systemic disease. PROCEDURE Peripheral blood lymphocytes were treated with gentamicin at concentrations 37.5 μg/mL, 112.5 μg/mL, 187 μg/mL, 375 μg/mL, or 750 μg/mL then stimulated to proliferate with concanavalin A (ConA). 4',6-diamidino-2-phenylindole (DAPI) and carboxyfluoroscein succinimidyl ester (CSFE) were used as markers of cell viability and cell proliferation, respectively. Following 5-day culture, live cell counts and CSFE fluorescent intensity data were collected via automated cell count and flow cytometry. The experimental design was duplicated using preservative-free gentamicin and a proprietary brand formulation. Statistical analysis was performed using two-way ANOVA with Tukey's multiple comparison test. RESULTS No statistically significant comparisons in CD3+ T-lymphocyte live cell counts and geometric mean fluorescent intensity of CSFE were identified between gentamicin concentrations or formulations. CONCLUSIONS Gentamicin had no effect on equine peripheral blood CD3+ T-lymphocyte cell viability and proliferation in concentrations ranging from "safe" to "retinotoxic" in relation to intravitreal injection volumes. Low-dose intravitreal gentamicin may not suppress the Th1- and Th17-mediated immune response.}, number={4}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Smith, Hannah L. and Berglund, Alix K. and Robertson, James B. and Schnabel, Lauren V. and McMullen, Richard J., Jr and Gilger, Brian C. and Oh, Annie}, year={2023}, month={Apr}, pages={347–354} } @article{himebaugh_robertson_weninger_gilger_ekesten_oh_2023, title={Ex vivo analysis of ultraviolet radiation transmission through ocular media and retina in select species}, volume={233}, ISSN={0014-4835}, url={http://dx.doi.org/10.1016/j.exer.2023.109550}, DOI={10.1016/j.exer.2023.109550}, abstractNote={The aim of this study was to assess the transmission of the ultraviolet (UV) radiation (200–400 nm) through intact enucleated globes of different species (dogs, cats, pigs, rabbits, horses, and humans) using spectrophotometry. Globes of cats (n = 6), dogs (n = 18), pigs (n = 10), rabbits (n = 6), horses (n = 10), and humans (n = 4) were analyzed. A 5–10 mm circular area of sclera and choroid from the posterior aspect of the globe was removed under a surgical microscope, leaving the retina intact in all species except the horse. Glass coverslips were added in horses and rabbits due to retinal and globe fragility. The %T of wavelengths from 200 to 800 nm were measured through the ocular media (cornea, aqueous humor, lens, and vitreous humor) and retina, and compared between species. The globes of cats and dogs allowed the most amount of UV radiation transmission, while those of pigs and humans allowed the least amount of UV radiation transmission. A small amount of UV radiation transmission through the ocular media was detected in the rabbit and horse. Results from this study will support further vision research that may be used to train companion, working, and service animals.}, journal={Experimental Eye Research}, publisher={Elsevier BV}, author={Himebaugh, Nicole E. and Robertson, James B. and Weninger, Keith and Gilger, Brian C. and Ekesten, Bjorn and Oh, Annie}, year={2023}, month={Aug}, pages={109550} } @article{murillo_souza teixeira campos_oh_smith_watanabe_2023, title={Primary ocular hemangiosarcoma in a dog}, volume={10}, ISSN={["2052-6121"]}, DOI={10.1002/vrc2.751}, abstractNote={A 10‐year‐old, male, neutered Boxer dog had an ulcerated mass covering nearly 90% of the left cornea. The dog had a 1year and 5months history of a previously removed left corneal hemangiosarcoma before clinical presentation. Visualisation and evaluation of the anterior chamber and internal ocular structures could not be performed because of the severe extension of the ocular mass. Enucleation of the left eye (OS) with extensive removal of the associated soft tissue was performed and submitted for histological examination. Histological findings confirmed corneal hemangiosarcoma with neoplastic extension to the limbus/conjunctiva. Corneal hemangiomas and hemangiosarcomas are rare in all domestic species. In dogs, a definitive cause for the development of corneal hemangiosarcomas is still undetermined. However, it is speculated that increased exposure to solar radiation and chronic inflammation‐inducing neovascularisation are predisposing factors. There was no evidence of mass recurrence or metastasis after 5 months of follow‐up.}, journal={VETERINARY RECORD CASE REPORTS}, author={Murillo, Daniel Felipe Barrantes and Souza Teixeira Campos, Maria Eduarda and Oh, Annie and Smith, Hannah and Watanabe, Tatiane Terumi Negrao}, year={2023}, month={Oct} } @article{stonex_zibura_andres_gilger_oh_2022, title={Polidocanol monotherapy for a superficial orbital venous malformation in a horse}, volume={25}, ISSN={1463-5216 1463-5224}, url={http://dx.doi.org/10.1111/vop.12997}, DOI={10.1111/vop.12997}, abstractNote={Abstract Objective To describe the use of 1% polidocanol as the sole treatment for a superficial orbital venous malformation in a horse. Animal A 23‐year‐old Welsh Cobb cross gelding with a distensible swelling affecting the left lower eyelid, and secondary palpebral margin abnormalities and superficial keratitis. Procedure Color flow Doppler ultrasonography revealed non‐pulsatile blood flow within the tortuous vascular network most consistent with a superficial orbital venous malformation appearing to involve the lateral palpebral and transverse facial veins. An intravenous catheter was placed within the lateral aspect of the venous malformation, and agitated saline was slowly injected into the vessel while simultaneously ultrasound imaging the medial aspect in which the bubbles were observed coursing across, consistent with lateral to medial flow. Contrast venography confirmed a corkscrew vessel along the ventral aspect of the orbital rim. Under standing sedation, 1% polidocanol solution was administered slowly through the intravenous catheter while manual pressure was applied on the medial and lateral aspects of the venous malformation. Results Ultrasonography performed immediately after administration of polidocanol confirmed venous stasis, and formation of a thrombus. No adverse side effects were noted. The venous malformation and associated palpebral margin abnormalities and superficial keratitis resolved at the time of re‐examination at 4 months. Conclusion and Clinical Relevance Polidocanol as the sole treatment for a superficial orbital venous malformation in a horse was well tolerated and led to clinical resolution. Sclerosant monotherapy may be a safe treatment option for superficial orbital venous malformations.}, number={5}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Stonex, Tara M. and Zibura, Ashley E. and Andres, Michael and Gilger, Brian C. and Oh, Annie}, year={2022}, month={Jun}, pages={412–418} } @article{hack_crabtree_avila_sutton_grahn_oh_gilger_bellone_2021, title={Whole-genome sequencing identifies missense mutation inGRM6as the likely cause of congenital stationary night blindness in a Tennessee Walking Horse}, volume={53}, ISSN={["2042-3306"]}, DOI={10.1111/evj.13318}, abstractNote={BACKGROUND The only known genetic cause of congenital stationary night blindness (CSNB) in horses is a 1378 bp insertion in TRPM1. However, an affected Tennessee Walking Horse was found to have no copies of this variant. OBJECTIVES To identify the genetic cause for CSNB in an affected Tennessee Walking Horse. STUDY DESIGN Case report detailing a whole genome sequencing approach to identify a causal variant. METHODS A complete ophthalmic exam, including an electroretinogram (ERG), was performed on suspected CSNB affected horse. Whole genome sequencing (WGS) data were generated from the case and compared to data from seven other breeds (n=29). One hundred candidate genes were evaluated for coding variants homozygous in the case and absent in all other horses. Protein modeling was used to assess the functional effects of the identified variant. A random cohort of 90 unrelated Tennessee Walking Horses and 273 horses from additional breeds were screened to estimate allele frequency of the GRM6 variant. RESULTS ERG results were consistent with CSNB. WGS analysis identified a missense mutation in metabotropic glutamate receptor 6 (GRM6) (c.533C>T p.Thr178Met). This SNP is predicted to be deleterious and protein modeling supports impaired binding of the neurotransmitter glutamate. This variant was not detected in 273 horses from three additional breeds. The estimated allele frequency in Tennessee Walking Horses is 10%. MAIN LIMITATIONS Limited phenotype information for controls and no additional cases with which to replicate this finding. CONCLUSIONS We identified a likely causal recessive missense variant in GRM6. Based on protein modeling, this variant alters GRM6 binding, and thus signaling from the retinal rod cell to the ON-bipolar cell, impairing vision in low light conditions. Given the 10% population allele frequency, it is likely that additional affected horses exist in this breed and further work is needed to identify and examine these animals.}, number={2}, journal={EQUINE VETERINARY JOURNAL}, author={Hack, Yael L. and Crabtree, Elizabeth E. and Avila, Felipe and Sutton, Roger B. and Grahn, Robert and Oh, Annie and Gilger, Brian and Bellone, Rebecca R.}, year={2021}, month={Mar}, pages={316–323} } @article{oh_foster_lunn_mowat_2019, title={Circulating neurohormone imbalances in canine sudden acquired retinal degeneration syndrome and canine pituitary-dependent hypercortisolism}, volume={33}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.15646}, abstractNote={Abstract Background Sudden acquired retinal degeneration syndrome (SARDS) has clinical similarity to pituitary‐dependent hypercortisolism (PDH) in dogs. Some studies have identified a greater frequency of SARDS in seasons with reduced daylight hours. Neurohormone imbalances contribute to retinal lesions in other species, warranting further study in dogs with SARDS. Hypothesis Dysregulation of circulating melatonin concentration is present in dogs with SARDS but not in dogs with PDH. Animals Fifteen client‐owned dogs with spontaneous SARDS (median time of vision loss 18 days), 14 normal dogs, and 13 dogs with confirmed PDH. Procedures Prospective case‐control study. ELISA on samples (obtained in the morning) for measurement of plasma melatonin and dopamine, serum serotonin, urine 6‐sulfatoxymelatonin (MT6s), and creatinine. Statistical analysis was performed using 1‐way ANOVA, Spearman correlation and receiver operator characteristic area under the curve analysis. Results There were no significant differences in circulating melatonin, serotonin or dopamine concentrations between the 3 groups, although the study was underpowered for detection of significant differences in serum serotonin. Urine MT6s:creatinine ratio was significantly higher in dogs with PDH (4.08 ± 2.15 urine [MT6s] ng/mL per mg of urine creatinine) compared with dogs with SARDS (2.37 ± .51, P < .01), but not compared with normal dogs. Conclusions and Clinical Relevance We have identified neurohormone differences between dogs with SARDS and PDH.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Oh, Annie and Foster, Melanie L. and Lunn, Katharine F. and Mowat, Freya M.}, year={2019}, month={Nov}, pages={2587–2594} } @article{oh_foster_williams_zheng_ru_lunn_mowat_2019, title={Diagnostic utility of clinical and laboratory test parameters for differentiating between sudden acquired retinal degeneration syndrome and pituitary‐dependent hyperadrenocorticism in dogs}, volume={22}, ISSN={1463-5216 1463-5224}, url={http://dx.doi.org/10.1111/vop.12661}, DOI={10.1111/vop.12661}, abstractNote={OBJECTIVE To identify discriminating factors, using clinical ophthalmic examination findings and routine laboratory testing, that differentiate dogs with early sudden acquired retinal degeneration (SARDS; vision loss <6 weeks' duration), age- and breed-matched control dogs, and dogs with pituitary-dependent hyperadrenocorticism (PDH). ANIMALS Client-owned dogs: 15 with SARDS with <6 weeks duration of vision loss, 14 age- and breed-matched control dogs, and 13 dogs with confirmed PDH. PROCEDURES Dogs underwent ophthalmic examination, electroretinography (ERG) fundus photography, and spectral-domain optical coherence tomography (SD-OCT) in addition to physical examination, urinalysis, serum biochemistry, complete blood count, and adrenocorticotrophic hormone (ACTH) stimulation testing. Statistical analysis was performed using receiver operating curve area under the curve analysis, principal component analysis with sparse partial least squares analysis, and one-way ANOVA. RESULTS Dogs with SARDS all had absent vision and ERG a- and b-waves. SD-OCT demonstrated that dogs with SARDS had significantly thicker inner retina, thinner outer nuclear layer, and thicker photoreceptor inner/outer segment measurements than either controls or dogs with PDH. Discriminating laboratory parameters between dogs with SARDS and PDH with high specificity included post-ACTH serum cortisol (<19.3 μg/dL), AST:ALT ratio (>0.343), and urine specific gravity (>1.030). CONCLUSIONS AND CLINICAL RELEVANCE We have identified significant discriminators between SARDS and PDH. This work provides the basis for future studies that could identify and examine dogs with SARDS prior to vision loss, which may extend the potential therapeutic window for SARDS.}, number={6}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Oh, Annie and Foster, Melanie L. and Williams, Jonathan G. and Zheng, Chaowen and Ru, Hongyu and Lunn, Katharine F. and Mowat, Freya M.}, year={2019}, month={Mar}, pages={842–858} } @article{mowat_wise_oh_foster_kremers_2019, title={In vivo electroretinographic differentiation of rod, short-wavelength and long/medium-wavelength cone responses in dogs using silent substitution stimuli}, volume={185}, ISSN={["1096-0007"]}, DOI={10.1016/j.exer.2019.05.013}, abstractNote={The canine species has dichromatic color vision comprising short-wavelength (S-) and long/medium (L/M-) wavelength-sensitive cones with peak spectral sensitivity of 429–435 nm and 555 nm respectively. Although differentiation of rod- and cone-mediated responses by electroretinogram (ERG) in dogs is commonly performed, and standards have been developed based on standards for human observers, methods to differentiate S- and L/M-cone responses in dogs have not been described. We developed flicker protocols derived from previously published rod and cone spectral sensitivities. We used a double silent substitution paradigm to isolate responses from each of the 3 photoreceptor subclasses. ERG responses were measured to sine-wave modulation of photoreceptor excitation at different temporal frequencies (between 4 and 56 Hz) and mean luminance (between 3.25 and 130 cd/m2) on 6 different normal dogs (3 adult female, and 3 adult male beagles) and one female beagle dog with suspected hereditary congenital stationary night blindness (CSNB). Peak rod driven response amplitudes were achieved with low frequency (4 Hz, maximal range 4–12 Hz) and low mean luminance (3.25 cd/m2). In contrast, peak L/M-cone driven response amplitudes were achieved with high frequency (32 Hz, maximal range 28–44 Hz) and high mean luminance (32.5–130 cd/m2). Maximal S-cone driven responses were obtained with low frequency stimuli (4 Hz, maximal range 4–12 Hz) and 32.5–130 cd/m2 mean luminance. The dog with CSNB had reduced rod- and S-cone-driven responses, but normal/supernormal L/M cone-driven responses. We have developed methods to differentiate rod, S- and L/M-cone function in dogs using silent substitution methods. The influence of temporal frequency and mean luminance on the ERGs originating in each photoreceptor type can now be studied independently. Dogs and humans have similar L/M cone responses, whereas mice have significantly different L/M responses. This work will facilitate a greater understanding of canine retinal electrophysiology and will complement the study of canine models of human hereditary photoreceptor disorders.}, journal={EXPERIMENTAL EYE RESEARCH}, author={Mowat, Freya M. and Wise, Elisabeth and Oh, Annie and Foster, Melanie L. and Kremers, Jan}, year={2019}, month={Aug} } @article{westermeyer_salmon_baynes_yeatts_khattab_oh_mowat_2019, title={Safety and efficacy of topically applied 0.5% and 1% pirfenidone in a canine model of subconjunctival fibrosis}, volume={22}, ISSN={["1463-5224"]}, url={https://doi.org/10.1111/vop.12619}, DOI={10.1111/vop.12619}, abstractNote={OBJECTIVE To evaluate tissue levels, safety, and efficacy of topical ophthalmic 0.5% and 1% pirfenidone in decreasing subconjunctival fibrosis. ANIMAL STUDIED Twelve normal beagle dogs PROCEDURES: A 5 × 1 mm diameter silicone disk was implanted subconjunctivally in one eye, and then dogs were treated with topical 0.5% pirfenidone (n = 9) in artificial tears or artificial tears alone (n = 3) for 28 days. To evaluate tissue drug levels, a single sample of tears, conjunctiva, and aqueous humor was collected 30 (n = 3), 90 (n = 3), and 180 min (n = 3) following administration of the last drop of pirfenidone, respectively. Fibrous capsule thickness and staining for Ki67 and fibroblast activation protein alpha (FAPα) were evaluated histologically. After a 2-week washout, the experiment was repeated in the opposite eye and using 1% pirfenidone. RESULTS Treatment with pirfenidone resulted in thinner fibrous capsules and decreased staining for FAPα with no adverse effects. The implant in one dog treated with pirfenidone extruded. There was no difference in tissue levels, capsular thickness, or staining for Ki67 or FAPα between dogs treated with 0.5% or 1% pirfenidone. CONCLUSIONS Pirfenidone may decrease fibrosis following glaucoma shunt surgery and can potentially be used indefinitely due to minimal side effects.}, number={4}, journal={VETERINARY OPHTHALMOLOGY}, author={Westermeyer, Hans D. and Salmon, Beth and Baynes, Ronald and Yeatts, James and Khattab, Ahlam and Oh, Annie and Mowat, Freya}, year={2019}, month={Jul}, pages={502–509} } @article{young_oh_williams_foster_miller_lunn_mowat_2018, title={Clinical therapeutic efficacy of mycophenolate mofetil in the treatment of SARDS in dogs-a prospective open-label pilot study}, volume={21}, ISSN={["1463-5224"]}, DOI={10.1111/vop.12545}, abstractNote={OBJECTIVE Sudden acquired retinal degeneration syndrome (SARDS) is a leading cause of irreversible blindness in dogs, yet no treatment has been objectively evaluated, or proven to be effective. Consensus of opinion is that SARDS is immune-mediated, although corticosteroid medications may exacerbate associated systemic signs. We examined the effect of sole-agent treatment with mycophenolate mofetil (MMF), a potent immunosuppressive medication unlikely to exacerbate associated systemic signs. ANIMALS STUDIED Ten client-owned dogs with SARDS prospectively recruited within 6 weeks of vision loss. PROCEDURES Clinical history, findings of systemic and ophthalmic examinations, blood parameters, visual navigation ability, electroretinography, and optical coherence tomography (OCT) were collected at baseline and at recheck after approximately 6 weeks of treatment with 10 mg/kg q 12 h of oral MMF. RESULTS Twenty percent of dogs (2/10) experienced side effects (diarrhea, vomiting, lethargy), which resolved with reduction in dose to 8 mg/kg q12 h. No significant changes in systemic signs, physical examination findings, or laboratory test results were detected at the recheck examination. Compared with baseline, visual ability significantly declined at the recheck examination, and the amplitude of a slow-onset negative waveform noted on dark-adapted electroretinography was reduced at the recheck examination. The outer retinal layers were significantly thinner at the recheck examination as measured by OCT. CONCLUSIONS Mycophenolate mofetil as a sole agent has no measureable positive effect on physical health, vision, or retinal structure following a 6-week trial period. Further studies are needed to evaluate other treatment options for SARDS.}, number={6}, journal={VETERINARY OPHTHALMOLOGY}, author={Young, Whitney M. and Oh, Annie and Williams, Jonathan G. and Foster, Melanie L. and Miller, William W. and Lunn, Katharine F. and Mowat, Freya M.}, year={2018}, month={Nov}, pages={565–576} } @article{oh_loew_foster_davidson_english_gervais_herring_mowat_2018, title={Phenotypic characterization of complete CSNB in the inbred research beagle: how common is CSNB in research and companion dogs?}, volume={137}, ISSN={["1573-2622"]}, DOI={10.1007/s10633-018-9653-y}, abstractNote={[[{:Label=>"PURPOSE"}, "Although congenital stationary night blindness (CSNB) has been described in a Japanese beagle dog research colony, certain clinical correlates with human CSNB have not yet been described, nor has an estimate of frequency of the condition been made in inbred and outbred beagle populations."], [{:Label=>"METHODS"}, "A beagle with CSNB obtained from a commercial research dog supplier in the USA and matched control dogs (n = 3) underwent examination, refraction, ocular imaging, assessment of visual navigation ability and detailed electroretinography (ERG). Retrospective review of ERGs in two independent groups of inbred (n = 15 and 537, respectively) and one group of outbred dogs (n = 36) was used to estimate CSNB frequency in these populations."], [{:Label=>"RESULTS"}, "In the affected dog, there were absent dark-adapted b-waves in response to dim-light flashes, severely reduced dark-adapted b-waves in response to bright-light flashes, and normal light-adapted b-waves with a-waves that had broadened troughs. Long-flash ERGs confirmed a markedly reduced b-wave with a preserved d-wave, consistent with cone ON-bipolar cell dysfunction. There was evidence of normal rod photoreceptor a-wave dark adaptation, and rapid light adaptation. In the wider beagle populations, five inbred beagles had a b/a wave ratio of < 1 in dark-adapted bright-flash ERG, whereas no outbred beagles had ERGs consistent with CSNB."], [{:Label=>"CONCLUSIONS"}, "The identified dog had clinical findings consistent with complete type CSNB, similar to that described in the Japanese colony. CSNB appears to be a rare disorder in the wider beagle population, although its detection could confound studies that use retinal function as an outcome measure in research dogs, necessitating careful baseline studies to be performed prior to experimentation."]]}, number={2}, journal={DOCUMENTA OPHTHALMOLOGICA}, author={Oh, Annie and Loew, Ellis R. and Foster, Melanie L. and Davidson, Michael G. and English, Robert V and Gervais, Kristen J. and Herring, Ian P. and Mowat, Freya M.}, year={2018}, month={Oct}, pages={87–101} }